Involvement of the Antimicrobial Peptide LL-37 in Human Atherosclerosis

Abstract

Objective-Antimicrobial peptides are effector molecules of the innate immune system. To understand the function of vascular innate immunity in atherosclerosis, we investigated the role of LL-37, a cathelicidin antimicrobial peptide, in the disease process. Methods and Results-Using real-time polymerase chain reaction, we found a 6-fold increase in human cationic antimicrobial protein 18/LL-37 transcript in human atherosclerotic lesions compared with normal arteries. Immunohistochemical analysis of atherosclerotic plaques showed that LL-37 was expressed mainly by macrophages and some endothelial cells. Western blot demonstrated existence of active LL-37 peptide and abundant proprotein in atheroma specimens. To understand the functional implication of LL-37 production in atherosclerosis, the transcription profile was assessed in endothelial cells treated with LL-37. Our data show that LL-37 induces expression of the adhesion molecule intercellular adhesion molecule-1 and the chemokine monocyte chemoattractant protein 1 in endothelial cells. Intriguingly, Chlamydia pneumoniae withstood the antimicrobial activity of LL-37 in vitro, although inflammatory response was induced on infection. Conclusion-LL-

Acute ST-Segment Elevation Myocardial Infarction is Associated with Decreased Human Antimicrobial Peptide LL-37 and Increased Human Neutrophil Peptide-1 to 3 in Plasma

“…LL-37 has been found in infiltrating macrophages and in some endothelial cells (ECs) in atherosclerotic lesions 14,15) . It may induce ICAM-1 and MCP-1 expression in cultured HUVECs 14) , and induce apoptosis of cultured VSMCs, which is known to be implicated in plaque rupture 15) .…”

“…It may induce ICAM-1 and MCP-1 expression in cultured HUVECs 14) , and induce apoptosis of cultured VSMCs, which is known to be implicated in plaque rupture 15) . PR-39, a cathelicidin family member in pigs, has been reported to play cardioprotective roles, such as limiting infarction size and proangiogenic function 16,17) ; however, there is lack of sequence and structural similarities between LL-37 and PR-39 16) .…”

F2L, a peptide derived from heme‐binding protein, inhibits LL‐37‐induced cell proliferation and tube formation in human umbilical vein endothelial cells

“…In addition, FPRL1 has been implicated in the tube formation of HUVECs stimulated with LL-37 [13,23]. Hence, we attempted to determine whether F2L alters tube formation in the LL-37-treated HUVECs.…”

Characterization of the psycho-neuro-immunological state in patients with coronary artery disease

“…The association observed between the MLR and LL-37 is not surprising, as monocytes and derived macrophages are known to release LL-37 in atherosclerotic lesions [98,101].…”

“…It can be expressed by monocytes/macrophages, neutrophils, natural killer cells and epithel cells [98][99][100]. It was found that LL-37 could be produced also by macrophages in atherosclerotic lesions [98,101].…”